Epithelial Barrier Theory

Pat Y, Ogulur I, Yazici D, et al. Tissue Barriers. 2023 Oct 2;11(4):2133877. Doi: 10.1080/21688370.2022.2133877. Epub 2022 Oct 19. PMID: 36262078; PMCID: PMC10606824.

Topic: summarizing the effects of human-induced environmental damage on global ecosystems and human health through the context of epithelial barrier theory

Pollution in the world and exposure of humans and nature to toxic substances is continuously worsening at a rapid pace. In the last 60 years, human and domestic animal health has been challenged by continuous exposure to toxic substances and pollutants because of uncontrolled growth, modernization, and industrialization. More than 350,000 new chemicals have been introduced to our lives, mostly without any reasonable control of their health effects and toxicity. A plethora of studies show exposure to these harmful substances during this period with their implications on the skin and mucosal epithelial barrier and increasing prevalence of allergic and autoimmune diseases in the context of the “epithelial barrier theory”. Exposure to these substances causes an epithelial injury with peri-epithelial inflammation, microbial dysbiosis and bacterial translocation to sub-epithelial areas, and immune response to dysbiotic bacteria. Here, we provide scientific evidence on the altered human exposome and its impact on epithelial barriers.

The change in human exposome: The main threats to nature and human health

Anthropocene refers to the current geological epoch in which human activities significantly affect the Earth’s geology and ecosystems. Since the industrial revolution, the proposed beginning of anthropogenic influences, the human impact on the nature has become more evident and the consequences such as anthropogenic climate change, habitat destruction, and environmental pollution are now threatening the Earth’s ecosystem and human health. 1,6,12-20 According to current reports, population sizes of species in the nature have decreased by 60% between 1970 and 2014 and extinction rates are 100 to 1000 times higher than previous background rates.21

The term exposome describes all the environmental exposures individuals are facing during their lifetime.4 These factors can be divided into three categories: general external environment, specific external environment, and host-dependent internal environment.22 The general external environment includes a wider socioeconomic environment such as climate, urban-rural environment, and educational level. However, specific external environment includes more individual factors such as lifestyle, pollutant exposure, and infections. However, the host-dependent internal environment includes both biological effects of external exposure and biological responses such as metabolic factors, inflammation, and oxidative stress.4,23,24 There have been alarming changes in the exposome in the last 70 years brought about by industrialization, urbanization, and modernization as exemplified by studies indicating human exposure to nearly 200,000-350,000 new chemicals.4,5,10 Since the 1950s, the amount of plastic production has increased nearly 200 times, and it is estimated that the total amount of plastic produced worldwide by 2017 reached approximately 8.3 billion metric tons.13,15,25 Today the human body is continuously exposed to a wide range of potentially harmful substances, such as PM, DEP, cigarette smoke, NP, MP, nanoparticles, ozone, nitric oxide (NO), nitrogen dioxide(NO2), carbon monoxide (CO), sulphur dioxide(SO2),  household cleaners, laundry and dishwasher detergents, toothpaste, surfactants and emulsifiers in processed food, and pesticides   (Figure 2). 1 Annual global deaths from pollution-related diseases are estimated at 9 million, still more than COVID-19-related deaths, mostly in underdeveloped countries.6,17

Ambient and indoor air pollution

Air pollution is one of our era’s biggest menaces as it contributes to climate change and is a leading cause of respiratory diseases.26 According to the World Health Organization’s (WHO) World Global Ambient Air Quality Database, 91% of the global population is exposed to poor air quality.27,28 Ambient air pollution alone is responsible for an estimated 3.7 to 4.2 million annual deaths worldwide. 6 Air pollution is a complex mixture of gaseous and particulate components. Gaseous components include NO, NO2, SO2, CO and ozone. 29 Air and aquatic PM originates from both natural and anthropogenic sources. Natural sources include dust, including desert dust, sea salt, and forest fires. In contrast, anthropogenic sources include traffic, power plants, factories, wood, and coal-burning emissions. 30 Studies suggest that air pollution aggravates cardiovascular and respiratory diseases and is associated with the development or progression of asthma, diabetes, reproductive, and various neurocognitive diseases.31-33 PM is classified according to particle size (PM0.1, PM2.5, and PM10). Epidemiological studies indicate that exposure to ambient PM pollution has increased over the past ten years coinciding with increased drug use, high fasting plasma glucose, and high body mass index.14 In the last 40 years, atmospheric black carbon concentration (which is a PM2.5) generated as a by-product of incomplete combustion of fossil fuels, biofuels, and biomass, has shown a substantial increase of 1.57 times (from 0.70 μg/m3 in 1980 to 1.10 ± 0.22 μg/m3 in 2019) with an annual increase by 1.52% in China.34 Moreover, it was reported that there was an independent association between short-term exposure to PM10 and PM2.5 and daily all-cause, cardiovascular, and respiratory mortality.35 According to a meta-analysis, there is a positive and statistically significant link between the onset of asthma and exposure to black carbon, NO2, PM2.5 and PM10, well-known traffic-related air pollution constituents. 36 Ambient air pollution, especially PM, is considered a neurotoxicant and impairs cognitive functions, learning abilities, and neurodevelopment. It is thought to be associated with depression, vascular dementia, and stroke. Along with urban PM, wildfire PM has also been associated with morbidity and mortality. An increased risk of hospitalization and emergency room visits for asthma, chronic obstructive pulmonary disease (COPD), and respiratory tract infection has been reported in individuals exposed to wildfire PM. 19 Among other air pollutants, exposure to oxides of nitrogen affects the central nervous system and contributes to neurological disorders.37 During COVID-19 restrictions, the atmospheric levels of air pollutants associated with traffic emissions including oxides of nitrogen, SO2, and CO, and primary PM levels decreased due to the quarantine and lock-down measures imposed by the governments. In contrast, secondary PM levels remained unchanged or even increased during the same period.38

Indoor pollution is a major problem, as pollution levels are often twice as high then outdoors and people spend 80-90% of their lives indoors.39 Household air pollution is estimated to be responsible for 2.9-4.3 million deaths per year worldwide.2 Thanks to social and economic development, household air pollution has declined in the last ten years. 14 Although the risk exposure to tobacco use is declining, it is still responsible for more than 8 million deaths annually of which 1.2 million are from second-hand smoking,40 mostly affecting low- and middle-income countries. 5,40

Micro- and nano- plastic pollution

The use of plastics has rapidly grown as these materials offer a low production cost and high stability and durability. However, plastic waste poses a threat to nature as most plastics are non-biodegradable. It is estimated that in 2015 globally 66-90 million metric tonnes of miss managed plastic waste are produced and every year 8 million tonnes of plastic waste are escaped to the oceans.25,41 When plastic waste enters the environment, it breaks down into small fragments and particles such as MPs (1 mm to 5 mm) and NPs (1 nm to 1000 nm).13,42 The degradation products can be detected in the air, water, and sediment.13,16 It is reported that nano- and MPs are harmful to aquatic species, such as zooplankton, bivalves, and small fish.13 Moreover, NPs can penetrate living organisms and eventually enter the human food chain.13,15 In addition, humans are exposed to airborne NPs through the airways and in contact with the skin.15 

Processed foods: harmful additives in foods

The modern food industry provides a wealth of supply and diversity made possible by the incorporation of food additives, such as synthetic colorants, preservatives, stabilizers, surfactants, emulsifiers, and texturizers. There is mounting evidence suggesting that processed foods that contain food additives and advanced glycation endproducts (AGEs) due to heat processing disrupt the integrity of the epithelial barrier, a key pathological feature in the development of allergic and autoimmune diseases.1,43  The consumption of processed food has been associated with all-cause mortality, obesity, metabolic syndrome and depression.44 In addition, food contamination is possible by contact with dishware that has residues from cleaning products, such as detergents and anionic surfactants.7,45,46

Anthropogenic climate change

Anthropogenic activities are responsible for global warming,47-49 with a mean temperature increase of 0.2°C per decade.18 A recent study predicts global warming of 2.6 °C (1.9 °C to 3.7°C) by 2100, taking into account only the current energy policies and measures being developed by the countries participating in the Paris agreement. Nonetheless, the authors noted that warming can be limited to 1.9–2.0°C if all the conditional and unconditional pledges of the Paris agreement are met in full and on time.50 The generation of large quantities of greenhouse gases has been a key driver of climate change, in particular carbon dioxide emissions. Moreover, deforestation cripples the Earth’s natural ability to remove atmospheric CO2, further aggravating global warming and causing extreme weather events.26,51 In the future, increases in morbidity and mortality are estimated due to climate change-related adverse effects such as heat-related illnesses, poor air quality, and undernutrition due to reduced food quality and security.18 It should be noted that the global risks from toxic pollution and climate change are highly correlated, with low- and middle-income countries being the most affected by both.17 Read more.